The increasing incidence of metabolic syndrome (hereinafter, also referred to simply as “MS”) arising from visceral obesity has become a social issue. MS refers to conditions were visceral obesity occurs in an individual with accumulations of other conditions such as impaired glucose tolerance, hyperlipidemia, and high-blood pressure, though the symptoms may be minor. The importance of MS has thus been recognized as the background of arteriosclerotic disease onset. According to the increasingly and internationally accepted MS diagnosis criteria introduced by the US National Cholesterol Education Program (NCEP), Adult Treatment Panel III (ATP III), MS is determined when at least three of the following criteria are met: (1) visceral fat diagnosed from a circumference at navel, (2) hypertriglyceridemia, (3) low HDL cholesteremia, (4) high-blood pressure, and (5) impaired glucose tolerance (NPL 1). MS diagnosis for Japanese is based on the criteria published by The Japanese Society of Internal Medicine in 2005. These criteria include visceral obesity as the essential item, and MS is determined when two or more of the following are met: high-blood pressure, abnormal lipid metabolism (hypertriglyceridemia and/or low HDL-cholesteremia), and fasting hyperglycemia (NPL 2).
The proposed criteria for determining visceral obesity as the essential conditions for MS include (a) a visceral fat area of 100 cm2 or more in computed tomography (CT), and (b) an abdominal circumference of 85 cm or more for men, and 90 cm or more for women in abdominal circumference measurement (NPL 3). CT measurement of visceral fat area can only be carried out in limited facilities, and involves cost and exposure problems. For these reasons, many facilities adopt abdominal circumference measurement for the determination of visceral obesity.
However, while the abdominal circumference measurement is simple, it is not necessarily sufficient in terms of measurement error and accuracy (NPL 4, 5), and development of newer diagnosis criteria is waited.
There are many reports concerning the involvement of genetic factors in MS (for example, NPL 6, 7, and PTL 1 to 4). NPL 6 introduces chromosomal sites related to MS. Further, PTL 1 describes a method for detecting specific polymorphism in Klotho gene as a method of determining the possibility of developing MS. PTL 2 describes a method for detecting specific polymorphism in angiopoietin-1 gene. PTL 3 describes a method for detecting specific polymorphism in McKusick-Kaufman syndrome gene. PTL 4 describes a method for detecting specific polymorphism in myosin IXA (AY09A) gene. However, a link to coiled-coil domain containing protein 3 (hereinafter, “CCDC3”) gene is not known.
PTL 5 reports FARS1 gene having the same sequence as the CCDC3 gene. It is also reported that increased diet in mice increases the body weight and FARS1 mRNA levels.
The anatomical location of the liver makes the liver the first target organ of the insulin secreted by the pancreas, and an organ that first uses the sugar that has entered the portal vein after absorption in the digestive tract. The liver also has contradictory functions synthesizing glycogen through the uptake of sugar during ingestion, and, on the other hand, producing and releasing sugar through glycogen decomposition and gluconeogenesis during a period of fasting. These functions are regulated in an effort to maintain the homeostasis in sugar metabolism. It is known that the sugar production in liver is modulated through activation of the insulin-induced glycogen synthesis in the hyperglycemia state, and through activation of glycogen decomposition and gluconeogenesis by the effects of substances such as glucagon, catecholamine, and cortisol in the hypoglycemic state.
While the sugar production and release in liver are regulated in this manner, there have been reports that liver glucose release amounts increase in cases of diabetes, an abnormal sugar metabolism disease. Specifically, an about 2-fold increase is confirmed in gluconeogenesis and liver glucose release amount in the diabetes model animal db/db mice (NPL 8), and an about 1.9-fold increase in liver glucose release amount is confirmed in human diabetes patients. It has been revealed that while 70% of liver glucose release amount originates in glycogen decomposition and 30% in gluconeogenesis in healthy individuals, 56% of the liver glucose release amount originates in gluconeogenesis in diabetes patients. These represent a strong indication that the increased liver glucose release amounts due to the acceleration of the gluconeogenesis system are involved in the hyperglycemia state of diabetes (NPL 9). Taken together, regulation of liver glucose release amount can be an important factor in considering diabetes therapy.